The overall objective of this integrated group of research studies is a more comprehensive understanding of the pathophysiology of manic-depressive disorders, particularly with regard to the complex interrelationships among clinical phenomenology, diagnosis, biological variables, and pharmacologic response. The studies are longitudinal; drug trials are double-blind. Major projects involve: (1) evaluation of tricyclic antidepressants which show specificity for a given monoamine neurotransmitter; (2) the study of phase shifts in sleep in cycling patients; (3) the manipulation of sleep as a possible treatment of depression; (4) the evaluation of pimozide, an experimental antipsychotic drug, as a relatively superior drug for "atypical" manias with schizoaffective features (5) the use of biological prediction of drug response including AER, MHPG, CSF, amine metabolites, neuroendocrine parameters and melatonin in blood and urine.